Fan Chen1, Dandan Chen1, Xinmei Zhao1, Shuai Yang1, Zhe Li2, Daniel Sanchis3, Liang Jin1, Xizhe Qiang1, Kaiye Wang1, Yitao Xu1, Yubin Zhang1, Junmei Ye4. 1. State Key laboratory of Natural Medicines, Department of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210006, China. 2. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular research Institute, Wuhan University, Wuhan 430060, China; Hubei key Laboratory of Cardiology, Wuhan 430060, China. 3. Institut de Recerca Biomedica de Lleida (IRBLleida)-Universitat de Lleida, Edifici Biomedicina-I. Av.Rovira Roure, 80, 25198 Lleida, Spain. 4. State Key laboratory of Natural Medicines, Department of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210006, China. Electronic address: junmeiye@cpu.edu.cn.
Abstract
OBJECTIVE: Obesity is associated with metabolic disorder and chronic inflammation that plays a crucial role in cardiovascular diseases. IL-6 is involved in regulating obesity-related lipid metabolism and inflammation. In this study, we sought to determine the role of IL-6 in high-fat diet (HFD)-induced cardiomyopathy and explore the signaling pathway. METHODS: Female, 5-week-old IL-6 knockout (KO) and littermate mice were fed a normal diet (ND, 10% fat) or HFD (45% fat) for 14 weeks. At the end of treatment, cardiac function was assessed by echocardiography. Adipose tissues and plasma were collected for further measurement. Immunohistology of CD68 was performed to detect inflammation in the heart. Masson's trichrome staining and Oil Red O staining was applied to evaluated cardiac fibrosis and lipid accumulation. Real-time PCR and Western immunoblotting analyses on heart tissue were used to explore the underlying mechanism. RESULTS: IL-6 KO mice displayed increased insulin resistance compared to WT mice at baseline. When fed HFD, IL-6 KO mice showed decreased gains in body weight and fat mass, increased insulin resistance relative to IL-6 KO mice feed ND. Furthermore, IL-6 KO mice developed cardiac dysfunction during HFD-induced obesity. Histological analysis suggested increased lipid accumulation, fibrosis and inflammation without affecting cardiac morphology during HFD treatment in the heart of IL-6 KO mice. Finally, IL-6 deficiency increased the phosphorylation of AMPK and ACC in the heart during HFD-induced obesity. CONCLUSION: Our results suggest that IL-6 contributes to limit lipid metabolic disorder, cardiac hypertrophy, fibrosis, inflammation and myocardium lipotoxicity during HFD-induced obesity.
OBJECTIVE:Obesity is associated with metabolic disorder and chronic inflammation that plays a crucial role in cardiovascular diseases. IL-6 is involved in regulating obesity-related lipid metabolism and inflammation. In this study, we sought to determine the role of IL-6 in high-fat diet (HFD)-induced cardiomyopathy and explore the signaling pathway. METHODS: Female, 5-week-old IL-6 knockout (KO) and littermate mice were fed a normal diet (ND, 10% fat) or HFD (45% fat) for 14 weeks. At the end of treatment, cardiac function was assessed by echocardiography. Adipose tissues and plasma were collected for further measurement. Immunohistology of CD68 was performed to detect inflammation in the heart. Masson's trichrome staining and Oil Red O staining was applied to evaluated cardiac fibrosis and lipid accumulation. Real-time PCR and Western immunoblotting analyses on heart tissue were used to explore the underlying mechanism. RESULTS:IL-6 KO mice displayed increased insulin resistance compared to WT mice at baseline. When fed HFD, IL-6 KO mice showed decreased gains in body weight and fat mass, increased insulin resistance relative to IL-6 KO mice feed ND. Furthermore, IL-6 KO mice developed cardiac dysfunction during HFD-induced obesity. Histological analysis suggested increased lipid accumulation, fibrosis and inflammation without affecting cardiac morphology during HFD treatment in the heart of IL-6 KO mice. Finally, IL-6 deficiency increased the phosphorylation of AMPK and ACC in the heart during HFD-induced obesity. CONCLUSION: Our results suggest that IL-6 contributes to limit lipidmetabolic disorder, cardiac hypertrophy, fibrosis, inflammation and myocardium lipotoxicity during HFD-induced obesity.
Authors: Yaqin Liang; Anna L Lang; Jian Zhang; Jing Chen; Kai Wang; Liya Chen; Juliane I Beier; Yan Qian; Lu Cai Journal: Chem Res Toxicol Date: 2018-05-10 Impact factor: 3.739
Authors: Pauline Souza Effting; Stella M S Brescianini; Helen R Sorato; Bruna Barros Fernandes; Giulia Dos S Pedroso Fidelis; Paulo Roberto L da Silva; Paulo César L Silveira; Renata T Nesi; Rolando B Ceddia; Ricardo A Pinho Journal: Arq Bras Cardiol Date: 2019-04-25 Impact factor: 2.000